912
Chapter 29: Psychopharmacological Treatment
Table 29.1-1
Glossary of Receptor Drug Interactions
Receptor Interaction Definition
Examples and Comments
Agonist (full agonist)
A drug or medication that binds to a specific
receptor producing an effect identical to that
usually produced by the neurotransmitter
affecting that receptor. Drugs are often
designed as receptor agonists to treat a variety
of diseases and disorders in which the original
neurotransmitter is missing or diminished.
Full agonists include opioids such as morphine,
methadone, oxycodone, hydrocodone, heroin,
codeine, meperidine, propoxyphene, and fentanyl.
Benzodiazepines act as agonists at the GABA receptor
complex.
Antagonist
A compound that binds to a receptor that blocks
or reduces the action of another substance
(agonist) at the receptor site involved.
Antagonists that compete with an agonist
for a receptor are
competitive antagonists.
Those that antagonize by other means are
noncompetitive antagonists.
Flumazenil is a competitive benzodiazepine receptor
antagonist. It competitively inhibits the activity at
the benzodiazepine recognition site on the GABA/
benzodiazepine receptor complex. It is the purest
antagonist synthesized.
Drugs used in the treatment of schizophrenia block
dopamine 2 receptors.
Examples of opioid antagonists include naltrexone and
naloxone.
Partial agonist
(mixed agonist)
A compound that (even when fully occupying
a receptor) possesses affinity for a receptor,
but elicits a partial pharmacological response
at the receptor involved. Partial agonists are
often structural analogs of agonist molecules.
If neurotransmitter concentrations are low,
partial agonists may behave as an agonist.
This is why these medications are sometimes
called mixed agonists.
Buprenorphine is a partial agonist that produces typical
opioid agonist effects and side effects, such as euphoria
and respiratory depression, but its maximal effects
are less than those of full agonists like heroin and
methadone.
When used at low doses buprenorphine produces sufficient
agonist effect to enable opioid-addicted individuals to
discontinue the drugs with fewer withdrawal symptoms.
Inverse agonist
An inverse agonist is an agent that binds to the
same receptor as an agonist for that receptor
but produces the opposite pharmacological
effect.
Several inverse agonists are currently in clinical
development. One particular example is R015-4513,
which is the inverse agonist of the benzodiazepine class
of drugs. R015-4513 and the benzodiazepines both
utilize the same GABA binding site on neurons, yet
R015-4513 has the opposite effect, producing severe
anxiety rather than the sedative and anxiolytic effects
associated with benzodiazepines.
Cannabinoid inverse agonists have been found to reduce
appetite, the opposite of the craving effect associated
with cannabis.
GABA,
g
-aminobutyric acid.
(Table by Norman Sussman, M.D.)
persistent, side effects include dry mouth that is associated
with noradrenergic reuptake inhibition or antimuscarinic activ-
ity. Some side effects appear later in treatment (
late-appearing
side effects
) and, sometimes, may be just the opposite of adverse
events early in treatment. For example, patients may typically
lose weight during early treatment with SSRIs, only to find, over
time, a reversal occurs, so that they gain weight. Similarly, early
activation or agitation may be followed by constant fatigue or
apathy. Because most data about new drugs come from short-
term studies, generally 8 weeks in duration, early-onset side
effects are overrepresented in product information and descrip-
tions of newly marketed information. It is essential that clini-
cians follow the letters to the editor sections of journals and
other sources of information to update their understanding of
the true side effect profile of a drug.
Adverse effects differ in their impact on compliance and
potential to cause harm. Depending on a patient’s threshold of
tolerance for a side effect and the impact on quality of life, side
effects can lead to drug discontinuation. Examples of serious side
effects include agranulocytosis (clozapine), Stevens-Johnson
syndrome (lamotrigine [Lamictal]), hepatic failure (nefazo-
done [Serzone]), stroke (phenelzine [Nardil]), and heart block
(thioridazine [Mellaril]). Overall, the risk of life-threatening
side effects with psychotropics is low. Drugs that carry such
a risk should be monitored more closely, and the prescribing
physician should take into account whether the potential clini-
cal benefits justify the additional risk. Any drug with a serious
risk, as reflected in a black box warning, is generally used less
extensively than would otherwise be the case.
In the case of haloperidol (Haldol) and other dopamine
receptor antagonists, long-term complications, such as tar-
dive dyskinesia, have been well documented. Emerging evi-
dence also suggests that the use of dopamine antagonists is
associated with a small increase in the risk of breast cancer
and that this is related to larger cumulative doses. In cases
in which serious risk is associated with a drug, closer medi-
cal monitoring of medication treatment is warranted. Because
the most widely used psychotropics, such as the SSRIs and
serotonin-dopamine antagonists, have only been in use since
the 1980s or 1990s, there is less certainty about long-term
effects, but no evidence indicates that side effects are not
merely extensions of those already evident during initial ther-
apy. It should also be kept in mind that most drugs used in the
treatment of chronic medical disorders have not been in use
